-
Free Radical Biology & Medicine Sep 2017Myeloperoxidase (MPO), an abundant protein in neutrophils, monocytes, and macrophages, is thought to play a critical role in the pathogenesis of various disorders...
Myeloperoxidase (MPO), an abundant protein in neutrophils, monocytes, and macrophages, is thought to play a critical role in the pathogenesis of various disorders ranging from cardiovascular diseases to cancer. We show that mesna (2-mercaptoethanesulfonic acid sodium salt), a detoxifying agent, which inhibits side effects of oxazaphosphorine chemotherapy, functions as a potent inhibitor of MPO; modulating its catalytic activity and function. Using rapid kinetic methods, we examined the interactions of mesna with MPO compounds I and II and ferric forms in the presence and absence of chloride (Cl), the preferred substrate of MPO. Our results suggest that low mesna concentrations dramatically influenced the build-up, duration, and decay of steady-state levels of Compound I and Compound II, which is the rate-limiting intermediate in the classic peroxidase cycle. Whereas, higher mesna concentrations facilitate the porphyrin-to-adjacent amino acid electron transfer allowing the formation of an unstable transient intermediate, Compound I*, that displays a characteristic spectrum similar to Compound I. In the absence of plasma level of chloride, mesna not only accelerated the formation and decay of Compound II but also reduced its stability in a dose depend manner. Mesna competes with Cl, inhibiting MPO's chlorinating activity with an IC of 5µM, and switches the reaction from a 2e to a 1e pathway allowing the enzyme to function only with catalase-like activity. A kinetic model which shows the dual regulation through which mesna interacts with MPO and regulates its downstream inflammatory pathways is presented further validating the repurposing of mesna as an anti-inflammatory drug.
Topics: Chlorides; Enzyme Assays; Enzyme Inhibitors; Humans; Kinetics; Leukocytes; Mesna; Models, Chemical; Peroxidase; Solutions; Taurine
PubMed: 28552694
DOI: 10.1016/j.freeradbiomed.2017.05.019 -
BMJ Case Reports Jun 2019Mesenchymal origin of primary thyroid angiosarcomas (TAS) is extremely rare and comprises less than 1% of primary thyroid cancer worldwide. While TAS are most commonly...
Mesenchymal origin of primary thyroid angiosarcomas (TAS) is extremely rare and comprises less than 1% of primary thyroid cancer worldwide. While TAS are most commonly occurring in the Alpine region, there are multiple reported cases of TAS in non-Alpine regions. Diagnosis of TAS is commonly made after thyroidectomy as cytologic diagnosis can be challenging due to paucity of cells, presence of necrosis and unawareness of the disease due to rarity. We report a case of primary TAS diagnosed by cytology in a 56-year-old man who presented with a sudden onset of left neck pain, swelling and haemoptysis. He was later noted to have suspicious nodules on both lobes of thyroid on ultrasound. Fine needle aspiration of thyroid nodules showed malignant epithelioid cells. The diagnosis of TAS was made based on positive endothelial markers such as thrombomodulin and CD31, with many pertinent negatives, including negative cytokeratins,thyroid transcription factor (TTF1), thyroglobulin, calcitonin and carcinoembryonic antigen (CEA).
Topics: Antibiotics, Antineoplastic; Doxorubicin; Hemangiosarcoma; Humans; Ifosfamide; Male; Mesna; Middle Aged; Thyroid Gland; Thyroid Neoplasms; Ultrasonography
PubMed: 31248893
DOI: 10.1136/bcr-2018-228862 -
Cureus Jan 2019Several commonly used chemotherapeutic agents, antibiotics, antivirals, and antiepileptic medications can cause partial or full Fanconi syndrome, disorders which can...
Several commonly used chemotherapeutic agents, antibiotics, antivirals, and antiepileptic medications can cause partial or full Fanconi syndrome, disorders which can generally be described as transport defects in the proximal renal tubule, associated with non-anion gap metabolic acidosis. Fanconi syndrome is underreported and therefore often missed in the clinical setting. Herein, we present a case report that details the course of a 64-year-old female with a history of stage IV undifferentiated pleomorphic sarcoma who after her sixth chemotherapeutic cycle (adriamycin, ifosfamide, and mesna) developed severe hypokalemia, hypophosphatemia, and proteinuria without glycosuria, eventually diagnosed with partial Fanconi syndrome. The aim of this report is to highlight the importance of routine serum and urine monitoring in patients undergoing therapy with potentially nephrotoxic agents to avoid potentially fatal renal nephrotoxicity, including partial and full Fanconi syndrome.
PubMed: 30937245
DOI: 10.7759/cureus.3947 -
FEMS Microbiology Reviews Jun 2003Nickel is an essential nutrient for selected microorganisms where it participates in a variety of cellular processes. Many microbes are capable of sensing cellular... (Review)
Review
Nickel is an essential nutrient for selected microorganisms where it participates in a variety of cellular processes. Many microbes are capable of sensing cellular nickel ion concentrations and taking up this nutrient via nickel-specific permeases or ATP-binding cassette-type transport systems. The metal ion is specifically incorporated into nickel-dependent enzymes, often via complex assembly processes requiring accessory proteins and additional non-protein components, in some cases accompanied by nucleotide triphosphate hydrolysis. To date, nine nickel-containing enzymes are known: urease, NiFe-hydrogenase, carbon monoxide dehydrogenase, acetyl-CoA decarbonylase/synthase, methyl coenzyme M reductase, certain superoxide dismutases, some glyoxylases, aci-reductone dioxygenase, and methylenediurease. Seven of these enzymes have been structurally characterized, revealing distinct metallocenter environments in each case.
Topics: Acetyl Coenzyme A; Bacteria; Gene Expression Regulation, Bacterial; Hydrogenase; Ion Transport; Mesna; Nickel; Protein Structure, Tertiary; Urease
PubMed: 12829270
DOI: 10.1016/S0168-6445(03)00042-1 -
Oncotarget Jul 2018Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing...
Doxorubicin-induced elevated oxidative stress and neurochemical alterations in brain and cognitive decline: protection by MESNA and insights into mechanisms of chemotherapy-induced cognitive impairment ("chemobrain").
Chemotherapy-induced cognitive impairment (CICI) is now widely recognized as a real and too common complication of cancer chemotherapy experienced by an ever-growing number of cancer survivors. Previously, we reported that doxorubicin (Dox), a prototypical reactive oxygen species (ROS)-producing anti-cancer drug, results in oxidation of plasma proteins, including apolipoprotein A-I (ApoA-I) leading to tumor necrosis factor-alpha (TNF-α)-mediated oxidative stress in plasma and brain. We also reported that co-administration of the antioxidant drug, 2-mercaptoethane sulfonate sodium (MESNA), prevents Dox-induced protein oxidation and subsequent TNF-α elevation in plasma. In this study, we measured oxidative stress in both brain and plasma of Dox-treated mice both with and without MESNA. MESNA ameliorated Dox-induced oxidative protein damage in plasma, confirming our prior studies, and in a new finding led to decreased oxidative stress in brain. This study also provides further functional and biochemical evidence of the mechanisms of CICI. Using novel object recognition (NOR), we demonstrated the Dox administration resulted in memory deficits, an effect that was rescued by MESNA. Using hydrogen magnetic resonance imaging spectroscopy (H-MRS) techniques, we demonstrated that Dox administration led to a dramatic decrease in choline-containing compounds assessed by (Cho)/creatine ratios in the hippocampus in mice. To better elucidate a potential mechanism for this MRS observation, we tested the activities of the phospholipase enzymes known to act on phosphatidylcholine (PtdCho), a key component of phospholipid membranes and a source of choline for the neurotransmitter, acetylcholine (ACh). The activities of both phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D were severely diminished following Dox administration. The activity of PC-PLC was preserved when MESNA was co-administered with Dox; however, PLD activity was not protected. This study is the first to demonstrate the protective effects of MESNA on Dox-related protein oxidation, cognitive decline, phosphocholine (PCho) levels, and PC-PLC activity in brain and suggests novel potential therapeutic targets and strategies to mitigate CICI.
PubMed: 30100992
DOI: 10.18632/oncotarget.25718 -
The Journal of International Advanced... Apr 2018MESNA (Sodium-2-mercaptoethanesulfonate) is a mucolytic substance that is used for chemically assisted tissue dissection in various surgical operations. The aim of this... (Comparative Study)
Comparative Study
OBJECTIVE
MESNA (Sodium-2-mercaptoethanesulfonate) is a mucolytic substance that is used for chemically assisted tissue dissection in various surgical operations. The aim of this study was to address the issue of possible neurotoxicity from topical administration of MESNA solution on the facial nerve. We used different concentrations of MESNA solution and evaluated their effects on facial nerve by histopathological and functional analysis.
MATERIALS AND METHODS
These groups were the saline administered group (control) (3 rats, 6 facial nerves), the 25% MESNA solution group (3 rats, 6 facial nerves), and the 100% MESNA solution group (3 rats, 6 facial nerves). Under general anesthesia (ketamine 150 mg/kg, xylocaine 4 mg/kg), the bilateral facial nerves of rats were dissected. The saline, 25% MESNA, and 100% MESNA solutions. Facial nerve functions of the rats were evaluated using mustachewhisker and blink reflex scores at day 20 days. On day 20, the rats were sacrificed and the buccal and marginal mandibular branches of the facial nerve were removed. The specimens were examined in terms of inflammation, granulation tissue, and foreign body reaction formation around the nerve. The functional and histopathological changes on facial nerves were compared between groups.
RESULTS
Mustache and blink reflex scores of the rats were 5 (normal) in both the control and study groups. There were no statistically significant differences between the three groups in terms of facial nerve functions (p=1.00). On histopathologic examination, the 25% and 100% MESNA groups had significantly more inflammation compared with the control group (p=0.038 and p=0.007, respectively). There were no statistically significant differences between the 25% and 100% MESNA groups in term of inflammation (p > 0.05). There were no statistically significant differences between the three groups in terms of foreign body reaction formation (p > 0.05).
CONCLUSION
Topical administration of MESNA solution onto the facial nerve causes increased inflammation in both the 25% and 100% concentrations. Nevertheless, it does not cause any facial nerve dysfunction.
Topics: Administration, Topical; Animal Experimentation; Animals; Facial Nerve; Inflammation; Mesna; Protective Agents; Rats; Rats, Wistar
PubMed: 29092802
DOI: 10.5152/iao.2017.3593 -
Pharmacotherapy 1997Hemorrhagic cystitis is a syndrome associated with certain disease states as well as exposure to drugs, viruses, and toxins. It manifests as diffuse bleeding of the... (Review)
Review
Hemorrhagic cystitis is a syndrome associated with certain disease states as well as exposure to drugs, viruses, and toxins. It manifests as diffuse bleeding of the endothelial lining of the bladder. Treatment includes intravesical, systemic, and nonpharmacologic therapies, all of which have advantages and disadvantages.
Topics: Alkylating Agents; Cyclophosphamide; Cystitis; Hematuria; Hemorrhage; Humans; Mesna; Urinary Bladder
PubMed: 9250547
DOI: No ID Found -
Clinical and Molecular Allergy : CMA May 2022Ifosfamide is an alkylating agent used in the treatment of a wide range of tumours. Because of known side effects it is usually administered in combination with mesna, a...
BACKGROUND
Ifosfamide is an alkylating agent used in the treatment of a wide range of tumours. Because of known side effects it is usually administered in combination with mesna, a thiol agent with uroprotective activity, to reduce them and increase the therapeutic dose. The most frequently administered regimens for ifosfamide are fractionated doses for 3 to 5 days, high-dose intravenous bolus, and continuous infusion over 24 to 72 h. Hypersensitivity reactions to ifosfamide plus mesna are not frequently described in the literature. Moreover, no reports exist concerning desensitization for this chemotherapy combination.
CASE PRESENTATION
A 47-year-old man with stage IV renal sarcoma was treated with the combination of ifosfamide and mesna every 3 weeks in a 4-consecutive-day infusion protocol. During the second cycle of chemotherapy, he presented acute cutaneous symptoms. A 12-step desensitization protocol was proposed in view of the lack of knowledge of the possible hypersensitivity reactions to this combination of chemotherapy agents, and the multiple difficulties found during the study of the case.
CONCLUSIONS
The 12-step desensitization protocol was well tolerated. Therefore, it is an appropriate and safe option in the case of suspected allergy to ifosfamide plus mesna.
PubMed: 35606850
DOI: 10.1186/s12948-022-00173-0 -
Indian Journal of Pharmacology 2014To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against...
OBJECTIVE
To investigate the possible protective effect of a single dose of ketamine and the synergistic effect between ketamine and 2-mercaptoethane sulfonate (mesna) against ifosfamide-induced hemorrhagic cystitis.
MATERIALS AND METHODS
35 adult female wistar rats were divided into five groups and pretreated with ketamine at 10 mg/kg and/or mesna 400 mg/kg 30 minutes before intraperitoneal injection of IFS (400 mg/kg) or with saline (control group). Hemorrhagic cystitis was evaluated 24 hours after IFS injection according to bladder wet weight (BWW), and microscopic changes, i.e. edema, hemorrhage, cellular infiltration, and urothelial desquamation. The markers of oxidative damage including nitric oxide (NO) and malondialdehyde (MDA) levels and the expressions of tumor necrosis factor alpha (TNF-α), interleukin 1-beta (IL-1β), inducible nitric oxide synthase (i-NOS) and endothelial nitric oxide synthase (e-NOS) were also assayed in the bladder tissues.
RESULTS
Pretreatment with ketamine alone or ketamine in combination with mesna reduced the IFS-induced increase of BWW (58,47% and 63,33%, respectively, P < 0.05). IFS- induced microscopic alterations were also prevented by ketamine with or without mesna (P < 0.05). In addition, also statistically insignificant, the bladder tissue expressions of IL-1β were lower in ketamine and/or mesna-receiving groups (P > 0,05). The parameters of oxidative stress, the NO and the MDA contents of the bladder tissues of the study groups were not different.
CONCLUSION
The results of the present study suggest that a single dose of ketamine pretreatment attenuates experimental IFS-induced bladder damage. It is therefore necessary to investigate ketamine locally and systematically with various dosing schedules in order to reduce the bladder damage secondary to oxazaphosphorine-alkylating agents and these results may widen the spectrum of ketamine.
Topics: Animals; Antineoplastic Agents, Alkylating; Biomarkers; Cystitis; Drug Therapy, Combination; Female; Hemorrhage; Ifosfamide; Immunohistochemistry; Ketamine; Mesna; Organ Size; Oxidative Stress; Rats, Wistar; Urinary Bladder
PubMed: 24741183
DOI: 10.4103/0253-7613.129301 -
Biochemistry May 2022Microbial anaerobic oxidation of alkanes intrigues the scientific community by way of its impact on the global carbon cycle, and its biotechnological applications.... (Review)
Review
Microbial anaerobic oxidation of alkanes intrigues the scientific community by way of its impact on the global carbon cycle, and its biotechnological applications. Archaea are proposed to degrade short- and long-chain alkanes to CO by reversing methanogenesis, a theoretically reversible process. The pathway would start with alkane activation, an endergonic step catalyzed by methyl-coenzyme M reductase (MCR) homologues that would generate alkyl-thiols carried by coenzyme M. While the methane-generating MCR found in methanogens has been well characterized, the enzymatic activity of the putative alkane-fixing counterparts has not been validated so far. Such an absence of biochemical investigations contrasts with the current explosion of metagenomics data, which draws new potential alkane-oxidizing pathways in various archaeal phyla. Therefore, validating the physiological function of these putative alkane-fixing machines and investigating how their structures, catalytic mechanisms, and cofactors vary depending on the targeted alkane have become urgent needs. The first structural insights into the methane- and ethane-capturing MCRs highlighted unsuspected differences and proposed some explanations for their substrate specificity. This Perspective reviews the current physiological, biochemical, and structural knowledge of alkyl-CoM reductases and offers fresh ideas about the expected mechanistic and chemical differences among members of this broad family. We conclude with the challenges of the investigation of these particular enzymes, which might one day generate biofuels for our modern society.
Topics: Alkanes; Anaerobiosis; Archaea; Catalysis; Mesna; Methane; Oxidation-Reduction; Oxidoreductases; Phylogeny
PubMed: 35500274
DOI: 10.1021/acs.biochem.2c00135